Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a 5-yr survival rate of 3%-5%. It is well accepted that stem-cell-associated gene expression plays a major role in cancerogenesis and tumor progression in different cancers. The catalytic subunit of human telomerase hTERT and the Piwi-family gene member Hiwi are both expressed in stem cells and in several malignant human tumors. But their mRNA expression in PDAC has not been investigated comprehensively yet. Therefore, we studied a cohort of 56 PDAC patients which were monitored for a mean observation time of 15.8 (range 1-61) months and whose median survival rate was 14 (range 1-49) months. We microdissected fresh frozen tumour tissues to highly enrich neoplastic cells, isolated mRNA, and applied a quantitative RT-PCR analysis for hTERT and Hiwi. Elevated mRNA levels for hTERT or for Hiwi were measured in 23 or 40 PDAC tissues, respectively. In survival analysis using multivariate Cox\#8217;s regression hazard regression analysis surprisingly low hTERT mRNA expression was correlated to a poor prognosis (RR=5.3; P=0.012) compared to high levels of hTERT. However, elevated Hiwi mRNA expression in PDAC was associated with a significantly increased risk for tumour-related death but only in men and not in women (RR=1.94; P=0.047). A combination of Hiwi and hTERT expression did not result in an additive effect on prognosis, suggesting that both genes may function in related pathways. Altogether, both hTERT (low) and Hiwi (increased) gene expression are associated with a shortened overall survival in PDAC patients and we suggest considering both as independent prognostic markers in PDAC.